Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAZ3MN)

• DTT Name: Beta-adrenergic receptor kinase 1 (ADRBK1)
• Synonyms: GRK2; G-protein coupled receptor kinase 2; BetaARK1; Beta-ARK-1; Beta ARK1
• Gene Name: GRK2
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: ARBK1_HUMAN
• TTD ID: T62548
• EC Number: EC 2.7.11.15
• Sequence:
  MADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRGEVTFEKIFS
  QKLGYLLFRDFCLNHLEEARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLAC
  SHPFSKSATEHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNV
  ELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNER
  IMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLHYHLSQHGVFSEADMRFYAAE
  IILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTHGYMAPE
  VLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPE
  LRSLLEGLLQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAA
  DAFDIGSFDEEDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARK
  KAKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSL
  LTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDAYREAQQLVQR
  VPKMKNKPRSPVVELSKVPLVQRGSANGL
• Function: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  Endocytosis (hsa04144)
  Glutamatergic synapse (hsa04724)
  Morphine addiction (hsa05032)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Activation of SMO (R-HSA-5635838)
  Calmodulin induced events (R-HSA-111933)

Molecular Interaction Atlas (MIA) of This DTT

5 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BDBM50173306	DMSTD28	N. A.	N. A.	Patented	[2]
US9493490, C	DMC1YR5	N. A.	N. A.	Patented	[3]
US9493490, D	DMUVC25	N. A.	N. A.	Patented	[3]
US9493490, E	DMFCIGE	N. A.	N. A.	Patented	[3]
US9493490, L	DMJDTSN	N. A.	N. A.	Patented	[3]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BetaARKct	DMN7DJ5	Discovery agent	N.A.	Investigative	[4]
PMID21596927C101	DM7JRHB	Discovery agent	N.A.	Investigative	[1]
PMID24210504C1o	DM4LEUT	Discovery agent	N.A.	Investigative	[5]

References

• [1] Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors. Mol Pharmacol. 2011 Aug;80(2):294-303.
• [2] G protein-coupled receptor kinase 2 inhibitors and methods for use of the same. US10023564.
• [3] Boron-containing small molecules. US9493490.
• [4] Gene-mediated inhibition of the b-adrenergic receptor kinase: a new therapeutic strategy for heart failure. Minerva Cardioangiol. 2001 Dec;49(6):389-94.
• [5] Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6711-6.